DOXAZOSIN FOR PTSD

DOXAZOSIN AS A TREATMENT FOR POST TRAUMATIC STRESS SYNDROME

The aims of this study is to determine the effects of treatment with doxazosin XL 16 mg/d combined with virtual reality (VR) exposure therapy on Post Traumatic Stress Disorder.

The effects of treatment with doxazosin XL 16 mg/d combined with virtual reality (VR) exposure therapy will be assessed in double-blind, placebo-controlled study. The study will enroll 30 participants. The investigators will use a within groups design in which all participants receive both placebo and doxazosin (N=16) with the order counterbalanced across participants. A second group of patients (N=16) will receive both 16mg perindopril and placebo instead of doxazosin/placebo.

Study Overview

• Status: Completed
• Conditions: PTSD
• Intervention / Treatment: Drug: Placebo; Drug: Perindopril; Drug: doxazosin

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be male OIF/OEF veteran or active duty. Males only are included in this small pilot study because we will not have sufficient sample size to analyze gender effects. Women will be included in subsequent studies
2. Be aged between 18 and 55 years
3. Meet DSM-IV TR criteria for PTSD
4. Meet inclusion criteria for VRE participation
5. Have vital signs as follows: supine blood pressure > 100/65 mm Hg, a seated blood pressure greater than 90/60 mm Hg, and an orthostatic change smaller than20 mm Hg systolic or 10 mm Hg diastolic on standing. Participants should not have hypertension (BP above 150/100)
6. Have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exceptions: (a) total bilirubin must be less than 2x upper limit of normal and ALT, AST, and alkaline phosphatase less than 3× the upper limit of normal and (b) kidney function tests (creatinine and BUN) within normal limits
7. Have a baseline ECG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant arrhythmias
8. Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator

Exclusion Criteria:

1. Have any history or evidence suggestive of seizure disorder or brain injury
2. Have neurological or psychiatric disorders, such as psychosis or bipolar illness as assessed by Structural Clinical Interview for DSM disorders (SCID); clinically significant organic brain disease or dementia or Axis I psychiatric illness other than PTSD that would interfere with study; acceptable history of suicide attempts within the past year and/or current suicidal ideation/plan
3. Have evidence of untreated or unstable medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
4. Have HIV and are currently symptomatic or are taking antiretroviral medication
5. Have any other illness or condition which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study
6. Dr. Newton (medical supervisor) will review potential participants' prescribed medication to make a final decision on eligibility. We anticipate that participants will be on a wide range of medications prescribed for PTSD. However, these treatments will unlikely interact with the doxazosin effects of this study. We will not ask participants to change their medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: doxazosin; Subjects will be randomized to receive either doxazosin XL or placebo. Participants will receive doses of study medication as over-encapsulated doxazosin XL or placebo dosed once in the morning. Study medication will be initiated as one capsule of doxazosin XL 4 mg or placebo given in the morning. The dose will be titrated up to 16 mg/d doxazosin XL or placebo as follows: Days 1-4: 4mg, Days 5-8: 8mg, Day 9-12: 12 mg, Days 13-16: 16 mg.	Drug: doxazosin
Active Comparator: perindopril; Subjects will be randomized to receive either perindopril 16mg or placebo for 8 days. Participants will receive doses of study medication as over-encapsulated perindopril or placebo dosed once in the morning.	Drug: Perindopril
Placebo Comparator: placebo; Subjects will be randomized to receive either doxazosin XL or placebo. Participants will receive placebo for doxazosin XL for 16 days and placebo for perindopril for 8 days.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measures are the Subjective Units of Distress Scale (SUDS) and PTSD Checklist (PCL) (m) ratings during VRE Iraq exposure.	0 and 16 days

Collaborators and Investigators

• Sponsor: Baylor College of Medicine

Publications and helpful links

General Publications

• Rodgman C, Verrico CD, Holst M, Thompson-Lake D, Haile CN, De La Garza R 2nd, Raskind MA, Newton TF. Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial. J Clin Psychiatry. 2016 May;77(5):e561-5. doi: 10.4088/JCP.14m09681.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): June 30, 2014
• Study Completion (Actual): June 30, 2014

Study Registration Dates

• First Submitted: December 2, 2014
• First Submitted That Met QC Criteria: December 3, 2014
• First Posted (Estimate): December 4, 2014

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: PTSD; treatment; virtual reality; doxazosin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Perindopril; Doxazosin
• Other Study ID Numbers: H-29283